Autoimmune neurologic diseases

Oral

Cross-talk Between Ms Disease-relevant B Cell Subsets and Microglia/macrophage: Implication in Ms Disease Progression

Thursday, June 15
5:45 PM - 7:00 PM

B cell depleting therapies efficiently decrease new multiple sclerosis (MS) relapses. Previously, we demonstrated that MS patients harbor abnormally higher proportions, as well as greater activation propensity, of pro-inflammatory effector B cells (Beff), producing high IL-6, TNF and GM-CSF levels compared to matching controls. B cells are also known to be fostered within the MS central nervous system (CNS), persisting within lesions and meningeal aggregates. The latter are adjacent to an important subpial cortical injury, involving microglia/macrophage activation and neuronal loss, which has now been strongly associated with progressive MS. However, how distinct B cells persist and interact with underlying CNS cells to potentially propagate to disease progression (a major unmet need) remains unknown. First, we demonstrated that M1 human microglia supernatants increase B cell activation (CD86 & CD95), while M2c-derived microglia supernatants were cytotoxic to B cells. In turn, Beff down-regulated IL-10 production by both microglia and macrophage through soluble products, and substantially enhanced the myeloid pro-inflammatory cytokine (IL-12, TNF & IL-6) responses, effects that were not seen by soluble products of anti-inflammatory (IL-10 expressing) B cells. Initial data also suggest that activated B cell soluble factors also increase myelin phagocytosis by microglia. These results indicate a potential bi-directional interaction between disease-relevant human B cell subsets and both resident CNS microglia and infiltrating myeloid cells, which may influence the propagation of MS-CNS compartmentalized inflammation associated with MS disease progression.

Hanane Touil

PhD student
McGill University, Montreal Neurological Institute

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    Rui Li

    Post-doc
    University of Pennsylvania

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      Craig Moore

      Assistant Professor
      Memorial University of New Foundland

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        Jack Antel

        Professor
        McGill University, Montreal Neurological Institute

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          Amit Bar-Or

          Melissa and Paul Anderson President’s Distinguished Professor
          University of Pennsylvania and McGill University

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            Cross-talk Between Ms Disease-relevant B Cell Subsets and Microglia/macrophage: Implication in Ms Disease Progression



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